PET imaging of norepinephrine transporter-expressing tumors using Br--bromobenzylguanidine

Watanabe, Shigeki; Hanaoka, Hirofumi*; Liang, J. X.; Iida, Yasuhiko*; Endo, Keigo*; Ishioka, Noriko

-iodobenzylguanidine (MIBG) labeled has been widely used for the diagnosis and radiotherapy of norepinephrine transporter (NET)-expressing tumors. This study demonstrated that a positron emitter Br labeled -bromobenzylguanidine (Br-MBBG) was prepared and evaluated as a potential PET tracer for imaging NET-expressing tumors. Br-MBBG was stable in vitro, but some time-dependent dehalogenation was observed after administration in normal mice. MBBG showed high uptake in PC-12 tumor cells, and this uptake was significantly decreased by the addition of NET inhibitors. In biodistribution, MBBG showed high tumor accumulation (32.0 18.6% ID/g at 3 h p.i.) and the tumor-to-blood ratio reached as high as 54.4 31.9. Tumor uptake of MBBG correlated very well with that of I-MIBG (r = 0.997), but not with F-FDG. MBBG-PET showed a very clear image of the transplanted tumor with high sensitivity, and the visualized lesion was different from that by FDG-PET. These results indicated that Br-MBBG would be a potential PET tracer for imaging NET-expressing neuroendocrine tumors, and could provide useful information for determining the indications for I-MIBG therapy.